Synthesis and Biological Evaluation of 3-Alkyl-1,5-Diaryl-1H-Pyrazoles as Rigid Analogues of Combretastatin A-4 with Potent Antiproliferative Activity.
A series of novel 3-alkyl-1,5-diaryl-1H-pyrazoles were synthesized as combretastatin A-4 (CA-4) analogues and evaluated for antiproliferative activity against three human cancer cell lines (SGC-7901, A549 and HT-1080). Most of the target compounds displayed moderate to potent antiproliferative activ...
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2015-01-01
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doaj-702ed481339c44128e6d89c0bcc9e62c2020-11-25T01:03:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01106e012871010.1371/journal.pone.0128710Synthesis and Biological Evaluation of 3-Alkyl-1,5-Diaryl-1H-Pyrazoles as Rigid Analogues of Combretastatin A-4 with Potent Antiproliferative Activity.Qile XuHuan QiMaolin SunDaiying ZuoXuewei JiangZhiyong WenZhiwei WangYingliang WuWeige ZhangA series of novel 3-alkyl-1,5-diaryl-1H-pyrazoles were synthesized as combretastatin A-4 (CA-4) analogues and evaluated for antiproliferative activity against three human cancer cell lines (SGC-7901, A549 and HT-1080). Most of the target compounds displayed moderate to potent antiproliferative activity, and 7k was found to be the most potent compound. Structure-activity relationships indicated that compounds with a trimethoxyphenyl A-ring at the N-1 position of the pyrazole skeleton were more potent than those with the A-ring at the C-5 position. Tubulin polymerization and immunostaining experiments revealed that 7k potently inhibited tubulin polymerization and disrupted tubulin microtubule dynamics in a manner similar to CA-4. Computational modelling demonstrated that the binding of 7k to the colchicine binding site on microtubules may involve a similar mode as CA-4.http://europepmc.org/articles/PMC4462585?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Qile Xu Huan Qi Maolin Sun Daiying Zuo Xuewei Jiang Zhiyong Wen Zhiwei Wang Yingliang Wu Weige Zhang |
spellingShingle |
Qile Xu Huan Qi Maolin Sun Daiying Zuo Xuewei Jiang Zhiyong Wen Zhiwei Wang Yingliang Wu Weige Zhang Synthesis and Biological Evaluation of 3-Alkyl-1,5-Diaryl-1H-Pyrazoles as Rigid Analogues of Combretastatin A-4 with Potent Antiproliferative Activity. PLoS ONE |
author_facet |
Qile Xu Huan Qi Maolin Sun Daiying Zuo Xuewei Jiang Zhiyong Wen Zhiwei Wang Yingliang Wu Weige Zhang |
author_sort |
Qile Xu |
title |
Synthesis and Biological Evaluation of 3-Alkyl-1,5-Diaryl-1H-Pyrazoles as Rigid Analogues of Combretastatin A-4 with Potent Antiproliferative Activity. |
title_short |
Synthesis and Biological Evaluation of 3-Alkyl-1,5-Diaryl-1H-Pyrazoles as Rigid Analogues of Combretastatin A-4 with Potent Antiproliferative Activity. |
title_full |
Synthesis and Biological Evaluation of 3-Alkyl-1,5-Diaryl-1H-Pyrazoles as Rigid Analogues of Combretastatin A-4 with Potent Antiproliferative Activity. |
title_fullStr |
Synthesis and Biological Evaluation of 3-Alkyl-1,5-Diaryl-1H-Pyrazoles as Rigid Analogues of Combretastatin A-4 with Potent Antiproliferative Activity. |
title_full_unstemmed |
Synthesis and Biological Evaluation of 3-Alkyl-1,5-Diaryl-1H-Pyrazoles as Rigid Analogues of Combretastatin A-4 with Potent Antiproliferative Activity. |
title_sort |
synthesis and biological evaluation of 3-alkyl-1,5-diaryl-1h-pyrazoles as rigid analogues of combretastatin a-4 with potent antiproliferative activity. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2015-01-01 |
description |
A series of novel 3-alkyl-1,5-diaryl-1H-pyrazoles were synthesized as combretastatin A-4 (CA-4) analogues and evaluated for antiproliferative activity against three human cancer cell lines (SGC-7901, A549 and HT-1080). Most of the target compounds displayed moderate to potent antiproliferative activity, and 7k was found to be the most potent compound. Structure-activity relationships indicated that compounds with a trimethoxyphenyl A-ring at the N-1 position of the pyrazole skeleton were more potent than those with the A-ring at the C-5 position. Tubulin polymerization and immunostaining experiments revealed that 7k potently inhibited tubulin polymerization and disrupted tubulin microtubule dynamics in a manner similar to CA-4. Computational modelling demonstrated that the binding of 7k to the colchicine binding site on microtubules may involve a similar mode as CA-4. |
url |
http://europepmc.org/articles/PMC4462585?pdf=render |
work_keys_str_mv |
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